This invention relates to a sustained release pharmaceutical dosage form, more particularly to a thermoplastic water-soluble transdermal dosage form for the sustained release of pharmaceuticals.
The object of much research in recent years has been to provide sustained release dosage forms for pharmaceuticals. Most pharmaceuticals have a rather narrow therapeutic range in which they are of optimum benefit. Above or below this range, the drug is ineffective and/or toxic. In administering a tablet or capsule of the drug, the concentration thereof in the body may at first exceed therapeutic levels. Drug concentration then gradually decreases with time, until it falls below the therapeutic range. Thus, the time during which the drug is present in effective amounts may be quite short.
Sustained release or controlled release dosage forms are of interest because they can deliver and maintain optimum therapeutic levels of a medicament for a longer period of time than a conventional dosage form. In addition, such dosage forms can often deliver the medicament without an initial release of a greater than a therapeutic amount thereof. An additional advantage is that by using a sustained release form, it is often possible to increase the time between successive administrations of the medicament, in effect reducing the frequency of administration.
Various sustained release dosage forms have been developed using cellulose ethers as a release controlling component. In U.S. Pat. No. 3,065,142 to Christiansen et al. it is taught to prepare a compressed matrix from a mixture of a powder methylcellulose or hydroxypropyl methylcellulose and an active medicament. Similar technology is also disclosed in U.S. Pat. Nos. 4,369,172 and 4,389,393. This dosage form has found great utility as an oral dosage form, a rectal suppository or intravaginal device. Unfortunately, however, these dosage forms have some properties which tend to limit their utility. For example, such dosage forms sometimes provide a high initial release of medicament which may in some instances be undesirable. Moreover, since the matrices in these dosage forms are not thermoplastic, the shape of such dosage forms is limited to those which can be prepared by compressing powdered cellulose ethers.
It is also known to make a sustained release dosage form by coating a pharmaceutical with a water-insoluble cellulose ether such as ethylcellulose, cellulose acetate phthalate, and the like. This approach has also been found to be useful in certain instances but the coating process employed is expensive and the shape and manner of use of the product dosage form are limited.
European Patent Publication No. 0050480 discloses a multiple layer sustained release dosage form for the delivery of prostaglandin. Such dosage form comprises outer release controlling layers of hydroxypropyl cellulose (HPC), a water-insoluble polymer such as polyvinyl acetate or cellulose acetate, and a minor amount of a plasticizer. This added release controlling layer optionally, but less preferably, contains a prostaglandin. This dosage form further contains a drug storing layer comprising a water-soluble polymer such as HPC, a prostaglandin and optionally a minor amount of a plasticizer in a water-insoluble polymer. In this system, the presence of a water-insoluble polymer is considered essential to provide controlled release of the prostaglandin.
Similarly, in European Patent Publication No. 0086093 there is disclosed a three-layer pharmaceutical dosage form. This form comprises outer layers of HPC and a minor amount of a plasticizer (optionally containing prostaglandin) and a middle drug storing layer comprised of a water-insoluble polymer, a water-soluble polymer such as polyvinylpyrrolidone or HPC, plasticizer and an organic acid. In this reference, the use of a water-insoluble polymer is considered necessary in order to provide a suitable sustained release dosage form. Moreover, this dosage form requires the formation of the respective film layers followed by lamination of the layers to form the final product. In addition, this dosage form is not said to be useful as other than a prostaglandin delivery system.
Another limitation of the foregoing dosage forms is that they are not useful as internal dosage forms such as tablets, suppositories, intravaginal devices, and the like. More recently, the use of transdermal delivery systems to deliver pharmaceuticals over an extended period has been developed. Most such systems employ a membrane at the diffusion controlling layer, in conjunction with a separate drug storing layer. Although transdermal delivery systems are becoming accepted as a means to administer a drug, it would be desirable to provide a transdermal system which is simple and inexpensive to manufacture.
In view of the deficiencies of the previously known sustained release forms, it would be desirable to provide an inexpensive, easily prepared, transdermal pharmaceutical dosage form which is widely applicable to diverse modes of pharmaceutical administration.